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• W2038693712 endingPage "967" @default.
• W2038693712 startingPage "954" @default.
• W2038693712 abstract "Transferrin (Tf) is an enigmatic metalloprotein that exhibits a profound conformational change upon binding of ferric ion and a synergistic anion (oxalate or carbonate). While the apo and holo forms of the protein have well-defined and stable conformations termed open and closed, certain aspects of Tf behavior imply the existence of alternative protein states. In this work, hydrogen/deuterium exchange was used in combination with mass spectrometry to map solvent-accessible surfaces of the iron-bound and iron-free forms of the N-terminal lobe of human serum Tf at both neutral and endosomal pH levels. While the deuterium uptake is significantly decelerated in the iron-bound state of the protein (compared with the apo form) at neutral pH, the changes are distributed very unevenly across the protein sequence. Protein segments exhibiting most noticeable gain in protection map onto the interdomain cleft region housing the iron-binding site. At the same time, protection levels of segments located in the bulk of the protein are largely unaffected by the presence of the metal. These observations are fully consistent with the notion of a metal-induced switch from the open to the closed conformation with solvent-inaccessible interdomain cleft. However, differences in the exchange behavior between the apo and holo forms of Tf become much less noticeable at endosomal pH, including the segments located in the interdomain cleft region. Intriguingly, a significant patch in the cleft region becomes slightly less protected in the presence of the metal, suggesting that the holoprotein exists in the open conformation under these slightly acidic conditions. The existence of a noncanonical state of holoTf was postulated several years ago; however, this work provides, for the first time, conclusive evidence that such alternative states are indeed populated in solution." @default.
• W2038693712 created "2016-06-24" @default.
• W2038693712 creator A5025273029 @default.
• W2038693712 creator A5070800706 @default.
• W2038693712 creator A5075218726 @default.
• W2038693712 date "2009-05-01" @default.
• W2038693712 modified "2023-09-23" @default.
• W2038693712 title "Existence of a Noncanonical State of Iron-Bound Transferrin at Endosomal pH Revealed by Hydrogen Exchange and Mass Spectrometry" @default.
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• W2038693712 doi "https://doi.org/10.1016/j.jmb.2009.03.044" @default.
• W2038693712 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2933096" @default.
• W2038693712 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19324057" @default.
• W2038693712 hasPublicationYear "2009" @default.
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